Inflammation & Complement Systems 2.pptx

Inflammation & complements system

1. Inflammation and Complement system

2. Overview Introduction Signs of Inflammation Types and Mechanisms of Inflammation Complement System

3. Overview of Inflammation Inflammation Acute inflammation Chronic inflammation Intravascular Extravascular Vascular Cellular 1-Vasoconstriction 2-Vasodilation 3-Increased Vascular Permeability 4- Stasis 1- Chemotaxis 2- Opsonization 3- Phagocytosis Transvascular 1-Margination 2- Rolling 3- Adhesion Transmigration/Diapedesis

4. Historical highlights Egyptian papyrus 3000BC Cornelius celsus 1 AD – CARDINAL SIGNS John Hunter (1973) Julius Conheim (1882) Galen 2 AD- functio laesa

5. Definition Inflammation is a response of vascularized tissues that-delivers leukocytes and molecules of host defense from the circulation to the sites of infection and cell damage in order to eliminate the offending agents

6. Cardinal Signs Of Inflammation

7. Infection Bacteria/virus/fungal/ Parasitic Trauma Thermal injury/toxicity Tissue necrosis ischemia Foreign bodies Splinter/dirt/suture Stimuli for Inflammation

8. S teps of the Inflammation R esponse Recognition of the injurious agent Recruitment of leukocytes Removal of the agent Regulation (control) of the response Repair (resolution)

9. Acute Inflammation

10. Reactions of Blood Vessels In Acute Inflammation

11. Vascular Permeability (Vascular Leakage) Endothelial Contraction Transcytosis Leukocyte Mediated Injury Mild Endothelial Injury Endothelial damage/Necrosis/ Endothelial death

12. Reactions of Leucocytes in Inflammation

13. Recognition of microbes and dead tissues

14. Neutrophil E xtracellular Tr aps (NETs)

15. Phagocytosis Recognition Engulfing Killing Opsonisation Actin polymerisation —> pseudopods—> Phagosome —> Phagolysosome O2 dependant killing O2 independant killing Primary Azurophilic granules Secondary Specific granules Tertiary Gelatnase granules

16. Steps of Phagocytosis

17. Mediators of Inflammation Cellular Plasma Preformed cellular Newly Formed cellular 1- Histamine 2- Serotonin 1- Nitric Oxide 2- Lipids 3- Proteins 1- Kinin system 2- Coagulation system 3- Complement system

18. Cell- derived mediators Vasoactive Amines: Histamine and Serotonin Preformed molecules and first mediators to be released in inflammation Antigen Membrane bound IgE Resting mast cell Activated mast cell Degranulating mast cell Antigen binds to IgE Activation Degranulation Releases histamine

19. Cell- derived mediators contd. Histamine Dilation of arterioles and increases permeability of venules Producing interendothelial gaps in venules(mediated via binding to H1 receptors on endothelial cells

20. Arachidonic acid metabolites

21. Role of Cytokines in Acute Inflammation

22. Plasma protein derived mediators Coagulation and kinin system

23. Morphologic Patterns of Acute Inflammation The morphologic hallmarks of acute inlammatory reactions are dilation of small blood vessels and accumulation of leukocytes and fluid in the extravascular tissue Serous Inflammation Fibrinous Inflammation Catarrhal inflammation Purulent Inflammation Exudation Cell poor Fluid - Effusion in cavity like Ascities , Pleural effusion, Bullae Deposition of fibrin in Extracellular space Eg- Acute Rheumatic Fever Seen in inflammation of mucus membrane Eg- Common cold Collection of Neutrophils Eg- Abscess,Ulcer

24. Chronic Inflammation

25. Types of Macrophages Activated macrophages Resident macrophages Classically activated Alternatively activated Derived from Yolk sac & Fetal Liver Mon onuclear Ph agocyte system / Reti uloendothelial system. H ost defense is to destroy microbes and promote the inlammatory response. Te minate inflammation and promote tissue repair.

26. Errors in Inflammation Leukocyte adhesion defect Defect in NADPH oxidase Defect in phagolysosome formation B2 integrin defect Sialyl lewis defect LAD-2 LAD-1 Chediak higaski syndrome Due to defect in LYST-1 gene Chronic granulomatous disease X linked recessive AR LAD-3 FERMT-3 gene defect

27. Complement System

28. Overview of Complement Systems C omplement C omponent Activation pathway Regulation of the Complement s ystem Complement Deficiencies Functions of Complement

29. Components of complement system

30. Designated as numerals (C1-C9), by letter symbols (factor D) , or by trivial names (homologous restriction factor) Peptide fragments formed by activation of component denoted by small fragments “a” = smaller fragment “b” = larger fragment Functional complexes with enzymatic activity designated by C4b2a,C3bBb

31. Activation Pathway

32. Structure of the C1 macromolecular complex

33. Alternative Pathway of Complement System

34. Initiator of Alternative Pathway

35. Functions of Complement System

36. Role of C3b in Opsonization

37. Regulation of Compliment System Before assembly of convertase activity After assembly of convertase activity Regulation at assembly of membrane-attack complex (MAC)

38. Complement deficiencies

39. Complement proteins Effects of deficiency C1q,C1r,C1s,C4,C2 Immune complex disease( SLE,GN,Vasculitis ) C3 Susceptible to capsulated bacteria Factor D and properdin Neisseria infections MBL Pyogenic infections in infants and children DAF,CD59 Autoimmune conditions(PNH) MAC Recurrent meningococcal and gonococcal infections C1INH Hereditary angioneurotic edema

40. Thank You